Estimation of Brain Amine Metabolism in Affective Illness: Cerebrospinal Fluid Studies Utilizing Probenecid

Abstract

In order to assess central serotonin and dopamine metabolism in patients with affective illness, cerebrospinal fluid amine metabolites 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were measured under base-line conditions and after probenecid administration. Since probenecid inhibits transport of 5 HIAA and HVA out of CSF, their accumulation after probenecid provides an estimate of amine turnover. The 5HIAA and HVA accumulations were increased by the respective amine precursors, tryptophan and L-dopa, and were decreased by inhibitors of synthesis, parachlorphenylalanine and α-methylparatyrosine. In depressed and manic patients, 5HIAA levels were similar to those in controls while probenecid-induced accumulations of 5HIAA tended to be lower than those in controls. HVA accumulation in depressed patients was low compared to that in controls. Amitriptyline and imipramine treatment significantly lowered 5HIAA accumulation, suggesting that the tricyclic antidepressants decrease central serotonin turnover.